71 results about "Aging-associated diseases" patented technology

The invention discloses a medicine for targeting senescent cells to stimulate endogenous immunity and application of the medicine, and relates to the field of biological medicine. The medicine provided by the invention can mediate the interaction between senescence cells and immune cells, enhance the endogenous immune function, and achieve the purposes of effectively removing senescence cells and improving senescence-related diseases. According to the functional molecule for targeted aging cell immune sensitization, one end of the molecule targets an aging cell membrane molecule, glutamic acid is used for marking the surface of an aging cell, coupling between an endogenous immune cell and the aging cell is mediated, and adhesion and removal of the aging cell by the immune cell are promoted. The molecule can regulate the immune microenvironment of senescence tissues, effectively reduce the number of positive senescence cells of senescence-related beta-galactosidase, reverse fibrosis and improve natural senescence phenotypes.

The invention belongs to the field of biomedicine, particularly relates to an age estimation method based on proteome data, and more particularly relates to a data set establishing method, an age estimation model training method, an age estimation method, an age estimation model or device, electronic equipment and a nonvolatile computer readable storage medium. And their use for assessing the biological age of a subject, the degree or rate of aging of the subject, the degree or rate of aging of a specific tissue / organ of the subject, the effect of aging intervention means, the risk of the subject to suffer from an aging-related disease and / or the therapeutic effect of the aging-related disease.

The invention relates to an application of a macrophage expressing an anti-uPAR chimeric antigen receptor in preparation of an anti-aging drug, and discloses a new application of the macrophage (CAR-M) expressing the anti-uPAR chimeric antigen receptor in senescence diseases, and the mechanism is that uPAR positive cells are specifically recognized and apoptosis of the uPAR positive cells is induced by targeting senescence cell surface antigen uPAR. According to the uPAR-CAR-M, a humanized anti-uPAR single-chain antibody is used as a chimeric antigen receptor recognition region, so that the chimeric antigen receptor has high specificity, and the chimeric antigen receptor is used for promoting the functions of macrophages by using a CD8 alpha transmembrane structural domain, a CD28 costimulatory molecule and a Megf10 sequence, so that a better killing effect is given to the CAR-M. The problems of inflammatory microenvironment caused by abnormal aggregation of senescence cells, chronic tissue damage and senescence-related disease treatment disorder are solved, and the application value for treating senescence-related diseases (such as osteoarthritis and the like) expressing uPAR is important.

The ageing of the population is a key issue in the modern societies. The inventors have therefore searched how to determine parameters linked with the biological age of the subject. This has led them to find that characterizing mitochondria in an area of the subject enables to deduce such parameters. For this, the inventors has developed a tool providing with characterizing parameters of a mitochondrion, and notably a morphology parameter of the mitochondrion and an ultrastructure parameter of the mitochondrion. This opens the way of exploiting the characterizing parameters of mitochondria for multiples applications, such as therapy, medicine screening or clinical follow-up for aging related disorders or mitochondrial disorders.

The invention discloses application of vimogib in preparation of a product for delaying and / or reversing T cell senescence, and belongs to the field of biological medicine. Experiments prove that the vimogii can enhance the lysosome function of T cells by enhancing the expression of TFE3 protein, so that the expression of anti-tumor and anti-virus related cytokines is enhanced, the lysosome function of senescent T cells of old people is improved, and the anti-tumor and anti-virus infection capability of the old people is enhanced. It is found for the first time that vimogii can improve the lysosome function of T cells by enhancing TFE3 protein expression, and the blank in the field is filled. According to the application, a new treatment thought is provided for improving immune aging related diseases of old people, the T cell lysosome function is enhanced by enhancing TFE3 protein expression through the medicine, then T cell aging is delayed and / or reversed, and an innovative application direction is provided for intervention of an aging immune system.

The invention belongs to the field of biomedicine, particularly relates to an age estimation method based on metabolic data, and more particularly relates to a data set establishing method, an age estimation model training method, an age estimation method, an age estimation model or device, electronic equipment and a nonvolatile computer readable storage medium. And their use for assessing the biological age of a subject, the degree or rate of aging of a subject, the effect of an aging intervention means, the risk of a subject having an aging-related disease, and / or the therapeutic effect of an aging-related disease.

The invention relates to a clinical index-based biological age evaluation system, a construction method and application, and belongs to the field of biological aging research. Firstly, clinical indexes of a subject are collected, a biological age estimation model is constructed based on the clinical indexes, and the biological aging speed is further calculated. The method can be used for identifying an individual which accelerates senescence or delays senescence, and risk prediction and crowd risk stratification of death and senescence related diseases are realized. According to the method, the nonlinear relationship between clinical indexes and the aging degree is considered, so that the biological age estimated by the method has a better prediction effect on the risk of death and new aging related diseases. The biological age and the biological aging speed are quantified based on the clinical indexes, measurement of the clinical indexes can be completed only through conventional physical examination and one-time blood sampling, the method has the advantages of being low in cost and convenient to use, the biological aging speed can be evaluated in time after physical examination, and health guidance opinions are provided for aging acceleration individuals.

Provided herein are novel 2,4-dinitrophenol (DNP) derivatives and prodrugs of formula (I), as modulators of mitochondria functions, as well as pharmaceutical compositions comprising a compound described above and methods thereof for treating various diseases and disorders associated with or related to mitochondrial dysfunctions (e.g., obesity, diabetes, insulin resistance, liver diseases, heart or renal failure, neurodegenerative diseases or aging related diseases).

The present application provides compounds that are PAPD5 inhibitors and are useful in treating a variety of conditions such as cancer, telomere diseases, viral infections, and aging-related and other degenerative disorders.

The invention discloses a ternary fusion polypeptide Col-TF-1 targeting senescence cells, a monoclonal antibody mAb SC-1 matched with the ternary fusion polypeptide Col-TF-1, an anti-aging composition containing the ternary fusion polypeptide Col-TF-1 and the monoclonal antibody mAb SC-1, and application of the ternary fusion polypeptide Col-TF-1 The fusion polypeptide is formed by connecting a targeting peptide for targeting a senescence cell surface uPAR receptor, a collagen active peptide for promoting collagen synthesis and an immunomodulatory peptide for activating NK cells in series through a flexible linker GGGGS, and the amino acid sequence is as shown in SEQ ID NO.1. The invention further discloses a preparation method of the fusion polypeptide. Through CDR region humanized reconstruction and pH sensitive histidine switch design, the affinity of the matched antibody mAb SC-1 is improved by 5 times in a subacid environment, and the ADCC effect is enhanced through fucose-deficient host cells. Experiments show that when the fusion polypeptide is combined with the antibody, the senescent cell clearance rate can reach 45.2%, the collagen density is increased by 83.5%, and the effect is obviously superior to that of a single drug. The composition provided by the invention can be applied to the fields of cosmetics, medical instruments, medicines and functional foods, and provides a new strategy for treatment of senescence-related diseases and development of anti-senescence products.

The invention relates to the technical field of biology, and discloses a method and equipment for dynamically detecting damage caused by ROS, and the method comprises the following steps: A, mixing ROS with a DNA skeleton nanostructure, and carrying out oxidative damage reaction; step B, within a period of time after the oxidative damage reaction occurs, sampling the morphological characteristics of the reaction product at multiple time points, and observing the change process of the morphological characteristics; c, according to the change process, the degree of damage caused by ROS to the DNA skeleton nanostructure is judged, and equipment capable of achieving the method comprises an ROS generation module, the DNA skeleton nanostructure, an oxidative damage reaction module and a data analysis module. The method can solve the problem that two types of ROS are difficult to visually distinguish in the prior art, can be used as a general system for evaluating the ROS regulation effect and performance of a nano material, and provides a new insight and method for deeply understanding the effect of ROS in biology and medicine, especially prevention and treatment of cancer and senescence related diseases.

The technology relates in part to compositions containing a cell penetrating peptide that can be used to selectively reduce a senescent cell population. The technology also relates to methods of treatment of ageing and ageing-associated diseases using a cell penetrating peptide to selectively reduce a senescent cell population.

According to the marker for systematic senescence detection and the application of the marker, large-scale samples of individuals of different age groups and health conditions are collected, comprehensive and deep analysis and experimental research are conducted, the key effect of elastin fragments in the senescence process is defined, and the elastin fragments are determined as the effective senescence detection marker. Meanwhile, the action mechanism of the elastin fragment as the marker is elasticated, including the close relation between the elastin fragment and senescence-related physiological indexes, cell signal channels and tissue and organ function changes, so that the senescence process can be accurately and effectively evaluated, and an accurate basis is provided for early diagnosis of various senescence-related diseases; the important value is realized in the fields of anti-aging research and clinical application. Meanwhile, a new way is opened up for developing a targeted intervention treatment strategy, and the method has a wide and good application prospect.

The application discloses application of a novel peptide UHP in preparation of a medicine for treating and / or preventing delayed aging, and belongs to the technical field of biological medicines.The novel peptide UHP is composed of 37 L-type amino acids including a transmembrane peptide HIV-TAT.It is proved by cell experiments that the novel peptide UHP significantly improves the aging phenotype of a HGPS cell model simulated by overexpression of progerin and a replicative senescent human normal fibroblast cell, reduces the SA-beta-gal positive cell proportion and the expression of SASP factors, and increases the expression levels of cell proliferation markers Ki67, Lamin B1 and Cyclin A2.It is proved by animal experiments that the novel peptide UHP can improve the progeria phenotype, body weight and exercise capacity of a progeria mouse, relieve fibrosis in multiple tissues, improve the skin aging phenotype, and prolong the survival period of the progeria mouse, thereby providing a new medicine selection for clinical treatment of aging-related diseases.

The invention discloses an application of N4-acetylcytidine (ac4C) in preparation of a medicine for delaying senescence and prolonging life. The method is realized by reducing the overall ac4C modification level of RNA (including rRNA, tRNA, mRNA, ncRNA and the like) in a living body, and specifically can be realized by inhibiting the expression of a key catalytic adapter protein THUMPD1 or using an inhibitor targeting THUMPD1 / ac4C. The invention also provides an application of a reagent for detecting the aging degree or diagnosing aging-related diseases, such as Alzheimer's disease, mitochondrial diseases, tumors and the like, in preparation of a detection kit based on the ac4C modification level of a specific target RNA molecule, and provides a brand new target spot and strategy for aging intervention and accompanying disease diagnosis and treatment.

The present invention provides novel 2,4-dinitrophenol (DNP) derivatives and prodrugs thereof as modulators of mitochondrial function. The present invention also provides pharmaceutical compositions comprising the compounds of the present invention and methods for using the same to treat various diseases and conditions associated with or related to mitochondrial dysfunction (e.g., obesity, diabetes, insulin resistance, liver disease, heart or kidney failure, neurodegenerative diseases, and aging-related diseases, including but not limited to sarcopenia, osteoporosis, etc.).

The present invention provides an miR 1978 inhibitor and use thereof in treating a senescence-related disease. The etiology of senescence-related diseases is proposed, and the overexpression of miR 1978 derived from the mitochondrial genome in cell line SHSY5Y is proven to give rise to decreased mRNA expression and protein levels of DHFR, KIF5C, and MSH3; as a result, SHSY5Y cell division is arrested in the G1 phase of the cell cycle, the number of cells in the G2 / M phase is significantly reduced, and meanwhile, the number of apoptotic cells is increased. Compared with a control, cells containing miR1978 have different nuclear DNA methylation states. A plurality of Alzheimer's disease-related proteins, such as APP, Tau, p-Tau, and APOE, or Parkinson's disease-related proteins, such as α-synuclein, are increased in the SHSY5Y cell line containing miR 1978, etc.

The invention discloses application of a targeted stimulating molecule in preparation of drugs, health care products and cosmetics for preventing and treating natural aging, and relates to the field of biological medicines. The molecule provided by the invention can mediate the interaction between senescence cells and immune cells, enhance the endogenous immune function, and achieve the purposes of effectively removing senescence cells and improving senescence-related diseases. One end of the functional molecule for targeted senescence cell immune sensitization targets senescence cell membrane molecules, glutamic acid is marked on the surfaces of senescence cells, coupling between endogenous immune cells and the senescence cells is mediated, and adhesion and removal of the senescence cells by the immune cells are promoted. The molecule can regulate the immune microenvironment of senescent tissues, effectively reduce the number of positive senescent cells of senescence-related beta-galactosidase, improve the natural senescence phenotype of an organism and recover the phenotype and function of senescent skin.

The present invention relates to a composition for preventing, alleviating, or treating neuronal aging-related diseases or disorders, the composition comprising extracellular vesicles derived from three-dimensional spheroid-type cell aggregates. The extracellular vesicles according to the present invention can reduce the expression of aging-related proteins and induce reactivation of aged neural stem cells, and thus can be used to treat various neuronal aging-related diseases or disorders by preventing, alleviating, or treating the aging of neurons.

The invention discloses an application of a substance taking Angpt18 as a target in preparation of a medicine for treating and delaying senescence, and the key regulation effect of an Angpt18 gene in the occurrence and progression process of normal senescence and senescence-related diseases is found for the first time through systematic and in-depth research; further experiments prove that by inhibiting or down-regulating the expression of the Angpt18 gene, the senescence process can be obviously delayed, and the expressions such as hypomnesia and behavioral ability decline in the senescence process can be effectively improved. Therefore, the Angpt18 gene can be used as an important intervention target for senescence and related diseases thereof, can be used for developing drugs with senescence delaying or treatment effects, can also be used as a biomarker for evaluating the senescence degree and diagnosing and prognosing the related diseases of senescence, and has wide application prospects and clinical transformation values.

The invention provides fusion protein comprising a SCAN domain bearing member of a zinc finger-containing protein, a fragment or variant thereof and a catalytically inactive RNA-guided endonuclease or a DNA adenine methyltransferase. Preferably, the fusion protein is for use in the treatment and / or prevention of cancer, neurodegenerative disease, neurodevelopmental disease, aging and aging-related disease.

The application discloses an engineered exosome targeting human urokinase-type plasminogen activator receptor uPAR and a preparation method and application thereof. Firstly, a high-affinity anti-human uPAR single-domain antibody VHH is prepared; then, a human umbilical cord mesenchymal stem cell engineering cell line expressing a VHH-PTGFRN fusion protein is constructed, and the engineered exosome is prepared and purified by combining three-dimensional hypoxic culture, chemical induction and size-exclusion chromatography technology. The engineered exosome comprises four comparative samples, wherein the core sample Exo^(VHH / miR) can simultaneously display the anti-uPAR VHH on the membrane surface to realize targeted delivery and enrich miR-193b-3p in the chamber to realize gene silencing, and the synergistic effect of the two can efficiently remove the uPAR high-expression senescent cells and inhibit the senescence-associated secretory phenotype SASP. The engineered exosome has the advantages of standardized preparation process, high yield and high purity, strong targeting, excellent curative effect and good safety, and can be used for preparing a treatment preparation for anti-aging and aging-related diseases, and has important clinical application value.

This invention provides a method for preparing and applying a nanosystem for regulating the osteogenic microenvironment. The nanosystem comprises catalase, lactate oxidase, and a strontium-containing mineralized nanolayer. Experiments demonstrate that this nanosystem can effectively treat bone aging-related diseases, and that catalase and lactate oxidase have a synergistic effect. This invention provides a novel treatment strategy for bone aging-related diseases and has broad prospects for clinical translation.

The present invention belongs to the field of biomedical technology, and specifically relates to siRNA that targets and inhibits the expression of the demethylase ALKB-1 gene or ALKBH1 gene and its application. The present invention uses Caenorhabditis elegans as a model, designs and synthesizes highly specific targeted siRNA for ALKB-1, and delivers it into the nematode body to achieve specific knockdown of ALKB-1, significantly delaying the aging process of Caenorhabditis elegans, and also has an improvement effect on aging-related diseases including Parkinson's. Through mechanism analysis, it was found that the anti-aging effect of specific siRNA targeted intervention of ALKB-1 is achieved by regulating the methylation modification of tRNA to affect protein homeostasis. The present invention provides a new reference method for the development of anti-aging drugs and gene therapy strategies based on siRNA targeted knockdown technology to intervene in the function of ALKB-1.

A method of treating an aging-related disorder includes identifying a subject having an aging-related disorder and administering to the subject a therapeutically effective amount of a desialylated O-glycosylated glycoprotein, wherein the therapeutically effective amount is between 0.1 mg / kg and 500 mg / kg with respect to a body weight of the subject. Also disclosed are methods for producing the desialylated O-glycosylated glycoprotein using a clonal cell lacking sialyltransferase activity.

Provided herein are pharmaceutical compositions and dietary supplements comprising vanadyl sulfate (VS) and method of use thereof for the induction of cell death in senescent cells. In particular. VS compositions find use in clearance of age-related and / or therapy-induced senescent cells and reduction / elimination of senescence associated secretory phenotype (SASP)-induced inflammatory environments in subjects. and therefore in the treatment / prevention of age-related conditions and / or cancer.

The present invention relates to a combination comprising: a carotenoid, a carotenoid metabolite, a carotenoid derivative, an analog or ester or salt thereof, and a second component selected from the following: an inhibitor of one or more BCL-2 anti-apoptotic protein family members, an activator of a pro-apoptotic BCL-2 family member, a senescent cell lysing agent and an inhibitor of a senescent phenotype. The present invention also relates to a cosmeceutical, a cosmetic or a pharmaceutical composition comprising the combination of the present invention, and its use in a cosmetic method and its medical use.

The invention relates to a construction method and application of a rapid aging animal model. According to the invention, the C5a protein is injected into the hippocampus of an animal in a brain stereotactic manner, so that the rapid aging animal model is successfully constructed. The rapid aging animal model construction method provided by the invention has high repeatability, and the rapid aging animal model can be efficiently and stably prepared; moreover, the rapid aging animal model constructed according to the method disclosed by the invention shows obvious and stable learning and memory disorder and aging-related phenotypes, including reduction of learning and memory ability, increase of aging marker level, damage of synapse-related protein and the like, has high representativeness, and can be applied to the rapid aging animal model. Therefore, the method is not only suitable for pathological mechanism research of senescence and related diseases or symptoms, but also provides a powerful tool for drug development of senescence related diseases or symptoms (such as cognitive hypofunction caused by senescence), and shows a good industrial application prospect.

The invention relates to the field of biological detection, in particular to a multi-omics combined screening cell senescence marker detection method and application thereof. According to the method, data of genomics, transcriptomics, proteomics and metabonomics are combined, and multi-dimensional data in the cell senescence process are subjected to high-throughput screening and integration by means of whole genome sequencing, RNA-Seq, a liquid chromatography-mass spectrometry technology and a gas chromatography-mass spectrometry technology. And adopting machine learning algorithms such as random forest, a support vector machine and deep learning to screen out key markers related to aging. The markers comprise genes, proteins and metabolites, and have relatively high sensitivity and specificity. Verification of different aging models proves that the screened markers change significantly in the aging process and can effectively reflect the biological characteristics of cell aging. The method provides new technical support and theoretical basis for research of an aging mechanism, early diagnosis of aging-related diseases and anti-aging treatment.